NURS 6521 Discussion: Comparing and Contrasting Pharmacologic Options for the Treatment of Generalized Anxiety Disorder

Generalized anxiety disorder is a chronic condition characterized by uncontrollable worrying, and of all anxiety disorders, GAD is the most least likely to remit (Rosenthal & Burchum, 2021). Depression is usually associated with GAD. According to Rosenthal & Burchum (2021), the hallmark of GAD is unrealistic or excessive anxiety about several events or activities. The FDA approved first-line medication choices include SSRI’s, SNRI’s and buspirone. The approved second line of medication is benzodiazepine. Antidepressants have a delay effect which can take several weeks to take effect, while benzodiazepine’s onset is rapid. The four main first-line medications include SSRI – Paroxetine (Paxil) & Escitalopram (Lexapro), SNRI – Venlafaxine (Effexor XR) & Duloxetine (Cymbalta).

Pharmacodynamics for SSRI’s according to Rosenthal & Burchum (2021), is by selectively blocking neuronal reuptake of serotonin 5-HT, a monoamine neurotransmitter. The reuptake concentration of 5-HT in the synapse increases, which activates the postsynaptic 5-ht receptors, this mechanism which is consistent with the theory that depression stems from a deficiency in monoamine-mediated transmission (Rosenthal & Burchum, 2021).

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Pharmacokinetics for SSRI’s, oral medication is well absorbed, even in the presence of food. They are metabolized by the liver primarily by CYP2D6, then followed by excretion in the urine (Rosenthal & Burchum, 2021). SSRI’s are known to cause sexual dysfunction including impotence and delayed orgasm, delayed ejaculation and decreased sexual interest. Weight gain is also associated with SSRI’s possibly due to the decreased sensitivity of 5-HT receptors that regulate appetite (Rosenthal & Burchum, 2021). MAOI’s are to be avoided when taking SSRI’s due to the risk of serotonin syndrome, which can be life threatening if left untreated.

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Pharmacodynamics for SNRI’s block the neuronal reuptake of serotonin and norepinephrine, with minimal effects of

other transmitters or receptors (Rosenthal & Burchum, 2021). The drug produces a powerful blockade of NE and 5HT reuptake and weak blockade of dopamine reuptake. There is evidence that SSRI’s are tolerated and considered safer to take.

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Pharmacokinetics for SNRI’s, orally they are well absorbed. The liver converts the medication to desvenlafaxine and active metabolite. The half-life is 5 hours for the parent drug and 11 hours for the active metabolite (Rosenthal & Burchum, 2021). SNRI’s are also known to cause sexual dysfunction. In addition, monitoring blood pressure is needed due to dose related diastolic hypertension. The patient will need to have their sodium levels monitored especially if taking a diuretic which will increase the chance of hyponatremia. As with SSRI’s MAOI’s will need to be avoided due to the risk of serotonin syndrome.

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In comparison according to Jakuboyski et al, (2018), higher doses of SSRIs within the therapeutic range are associated with greater treatment benefit, whereas higher doses of SNRIs are not.

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According to Ruhe et al, (2019), Because the prevalence of antidepressant withdrawal symptoms is unknown and not all patients require dose reductions to discontinue antidepressants, three risk-factors that are consistently reported in the literature to indicate an increased risk of antidepressant withdrawal symptoms: (1) dosing above the minimal effective dose to reach efficacy, (2) antidepressant withdrawal symptoms when a dose was missed or during strategic treatment interruption, and (3) earlier failed attempts to discontinue the SSRI or SNRI.

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Benzodiazepine, though the second line in treatment for anxiety due to the risk of dependence, is the first line for an acute anxiety attack. According to Rosenthal & Burchum (2021), benefits derive from enhancing responses to GABA, an inhibitory neurotransmitter. Benzodiazepines should be avoided in patients with a known history of drug abuse.

References

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Jakubovski, E., Johnson, J. A., Nasir, M., Müller-Vahl, K., & Bloch, M. H. (2018). Systematic Review and meta-analysis: Dose-response curve of ssris and Snris in anxiety disorders. Depression and Anxiety, 36(3), 198–212. https://doi.org/10.1002/da.22854

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Rosenthal, L. D., & Burchum, J. R. (2021). Lehnes pharmacotherapeutics for advanced practice nurses and physician assistants. St. Louis, MO: Elsevier.

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Ruhe, H. G., Horikx, A., van Avendonk, M. J., Groeneweg, B. F., & Woutersen-Koch, H. (2019). Tapering of SSRI treatment to mitigate withdrawal symptoms. The Lancet Psychiatry, 6(7), 561–562. https://doi.org/10.1016/s2215-0366(19)30182-8

Generalized anxiety disorder (GAD) is a long-term condition characterized by excessive or exaggerated anxiety and fear of life events for no apparent reason. Treatment for GAD can be anything from counseling to medications like antidepressants and anxiolytics. Physicians prescribe anxiolytics to stop or prevent anxiety symptoms through quieting nerve cell activity in the brain (Bandelow et al., 2017). Treatment choices for GAD are based on how significant the problem is affecting the ability of the patient’s body to carry out daily activities. The main treatment options for GAD are Medications or pharmacology, and psychotherapy (Robichaud et al., 2019).

Short-term drugs for episodic anxiety symptoms help for transitioning to other anti-anxiety drugs including antidepressants like the serotonin-norepinephrine reuptake inhibitor (SNRI), selective serotonin reuptake inhibitor (SSRI), and tricyclic antidepressant (TCA). Antidepressants are often used as the first-line treatment for GAD because of their mechanism of action with the downregulation of noradrenalinergic receptors. Also, unlike benzodiazepines, it may be used without causing tolerance. The pharmacodynamic effects of FDA-approved drugs depend on the class to which they belong. Benzodiazepines bind to the gamma aminobutyric acid (GABA) receptors of the brain and enhance the GABA-medicated synaptic inhibition hence lowering abnormal excitement of the brain (Beck & Beck, 2018).

Pharmacokinetically, diazepam is rapidly absorbed orally and is widely bound and distributed to plasma proteins, where it is metabolized by cytochrome p450 enzymes, bound to glucuronide, and excreted in the urine. Many traditional diazepines are metabolized in the liver and, when combined with drugs that block their effects, increase blood levels and can cause side effects. Examples include alprazolam and clonazepam. Another class of drug is buspirone, whose effects are related to the neurotransmitter serotonin. Unlike diazepam, it promotes noradrenalinergic and dopaminergic cell firing while having different effects on serotonergic activity. Therefore, their mechanism of action rejects the notion that there is only one neurotransmitter that mediates fear. It is orally absorbed, bound to serum albumin, distributed, metabolized in the liver, and then excreted in the urine. The third class is Vistaril. It works by blocking histamine receptors and treating insomnia GAD. It falls into any histamine class and can be administered as an oral capsule/tablet or an injectable liquid. The drug is rapidly absorbed in the gastrointestinal tract and its effects are notable within the first thirty minutes. Despite its rapid action it is often associated with a lot of sedation (Beck & Beck, 2018). Among the pharmacotherapeutic options for treating GAD are antidepressants including the SSRIs e.g., Lexapro and Paxil, and SNRIs such as Duloxetine and venlafaxine. Alternatively, physicians may consider cognitive psychological counseling depending on contraindications based on the genetic predisposition of the patient, age, or situation.

References

Bandelow, B., Michaelis, S., & Wedekind, D. (2017). Treatment of anxiety disorders. Dialogues in clinical neuroscience, 19(2), 93. Doi: 10.31887/DCNS.2017.19.2/bbandelow

Beck, D. A., & Beck, C. L. (2018). Anxiolytics. In Clinical Psychopharmacology for Neurologists (pp. 73-95).

Robichaud, M., Koerner, N., & Dugas, M. J. (2019). Cognitive behavioral treatment for generalized anxiety disorder: From science to practice. Routledge. https://www.taylorfrancis.com/books/mono/10.4324/9781315709741/cognitivebehavioral-treatment-generalized-anxiety-disorder-melisa-robichaud-naomi-koernermichel-dugas

Week 8 Discussion

COLLAPSE

Pharmacokinetics is the study of drug movement throughout the body. There are four basic pharmacokinetic processes: absorption, distribution, metabolism, and excretion. Pharmacodynamics is the study of the biochemical and physiologic effects of drugs in the body (Rosenthal, L. D., & Burchum, J, R. 2021 pg. 13 & 22). Generalized anxiety disorder is chronic condition that is uncontrollable worrying. Most patients with this disorder also have another psychotic disorder called depression. The hallmark of GAD is unrealistic or excessive anxiety about several events or activities that last 6 months or longer (Rosenthal, L. D., & Burchum, J, R. 2021 pg. 243). Treatments used for this disorder can be nondrug or drug therapy. The non-drug approach could be supportive therapy, cognitive behavioral therapy, biofeedback, or relaxation therapy. All these therapies can help with coping skills with anxiety provoking situations (Rosenthal, L. D., & Burchum, J, R. 2021 pg. 243). If drugs are needed the 1^st line are SRRI and SNRI which the most used are Cymbalta, Paxil, Lexapro, Effexor XL. The 2^nd line benzodiazepines are used for immediate stabilization when anxiety is severe. Buspirone is used as benzo (McCance & Huether, pg. 605). The 1^st line drugs are used on a continuous basis with the supervision of a psychiatrist and the benzos are used for as needed purposes.

Reference:

Rosenthal, L. D., & Burchum, J. R. (2021). Lehne’s pharmacotherapeutics for advanced practice nurses and physician assistants (2^nd ed.) St. Louis, MO: Elsevier.

McCance, K. L. & Huether, S. E. (2019). Pathophysiology: The biologic basis for disease in adults and children(8th ed.). St. Louis, MO: Mosby/Elsevier

Pharmacology for Psychological Disorders

COLLAPSE

There have been several studies conducted to explore the effect of drugs on the central nervous system. The primary aim of these studies have been to establish penetration of blood-brain barrier, explore the target engagement and the mechanism involved. Anxiety disorders are the most prevalent psychiatric disorders and a leading cause of mental disability. Selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) are the first line of treatment for Generalized Anxiety Disorders (GAD). The recommended duration of treatment may vary anywhere from 3 months to 1 year or longer depending on the client’s compliance, the conditions and other influencing factors. These medications are well tolerated and the side effects and adverse effects are short lived or managed with the use of adjunctive treatment. The tricyclic antidepressants were the first classes of medications used for anxiety disorders that act as reuptake inhibitors of transporters of serotonin and norepinephrine. However despite its efficacy to SSRIs they are less prescribed due to side effects including sedation, weight gain, dry mouth, arrhythmias, and risk of mortality with overdose(Bakker, Balkom, & Spinhoven, 2002). Mixed antidepressants such as Mirtazapine has a broad pharmacological effect and Bupropion is approved for the treatment of MDD as it acts as a dopamine norepinephrine reuptake inhibitor. Although there is increasing stigma around the use of Benzodiazepines they have been a longstanding treatment for anxiety and are still widely prescribed class of psychiatric medications (Agarwal, & Landon, 2019). The most studied antihistamine is Hydroxyzine. It is the only antihistamine that has been approved by FDA for use in anxiety. Certain Beta adrenergic antagonist although not approved for any psychiatric indications has been widely prescribed for social anxiety disorder and performance anxiety. The only antipsychotic which is FDSA approved for anxiety treatment is a first generation antipsychotic, trifluoperazine.

References

Agarwal, S. D., & Landon, B. E. (2019). Patterns in Outpatient Benzodiazepine Prescribing in the United States. JAMA Network Open, 2(1), e187399. https://doi.org/10.1001/jamanetworkopen.2018.7399

Bakker, A., van Balkom, A. J. L. M., & Spinhoven, P. (2002). SSRIs vs. TCAs in the treatment of panic disorder: a meta-analysis. Acta Psychiatrica Scandinavica, 106(3), 163–167. https://doi.org/10.1034/j.1600-0447.2002.02255.x

Garakani, A., Murrough, J. W., Freire, R. C., Thom, R. P., Larkin, K., Buono, F. D., & Iosifescu, D. V. (2020). Pharmacotherapy of Anxiety Disorders: Current and Emerging Treatment Options. Frontiers in Psychiatry, 11. https://doi.org/10.3389/fpsyt.2020.595584

Comparing and Contrasting Pharmacologic Options for the Treatment of Generalized Anxiety Disorder

Psychological disorders, such as depression, bipolar, and anxiety disorders can present several complications for patients of all ages. These disorders affect patients physically and emotionally, potentially impacting judgment, school and/or job performance, and relationships with family and friends. Since these disorders have many drastic effects on patients’ lives, it is important for advanced practice nurses to effectively manage patient care. With patient factors and medical history in mind, it is the advanced practice nurse’s responsibility to ensure the safe and effective diagnosis, treatment, and education of patients with psychological disorders.

Generalized Anxiety Disorder is a psychological condition that affects 6.1 million Americans, or 3.1% of the US Population. Despite several treatment options, only 43.2% of those suffering from GAD receive treatment. This week you will review several different classes of medication used in the treatment of Generalized Anxiety Disorder. You will examine potential impacts of pharmacotherapeutics used in the treatment of GAD. Please focus your assignment on FDA approved indications when referring to different medication classes used in the treatment of GAD.

Also Read:

NURS 6521: Basic Pharmacotherapeutic Concepts

Resources

Be sure to review the Learning Resources before completing this activity.
Click the weekly resources link to access the resources.

WEEKLY RESOURCES

To Prepare:

Review the Resources for this module and consider the principles of pharmacokinetics and pharmacodynamics.
Reflect on your experiences, observations, and/or clinical practices from the last 5 years and think about how pharmacokinetic and pharmacodynamic factors altered his or her anticipated response to a drug.
Consider factors that might have influenced the patient’s pharmacokinetic and pharmacodynamic processes, such as genetics (including pharmacogenetics), gender, ethnicity, age, behavior, and/or possible pathophysiological changes due to disease.
Think about a personalized plan of care based on these influencing factors and patient history with GAD.

By Day 3 of Week 8

Post a discussion of pharmacokinetics and pharmacodynamics related to anxiolytic medications used to treat GAD. In your discussion, utilizing the discussion highlights, compare and contrast different treatment options that can be used.

By Day 6 of Week 8

Read a selection of your colleagues’ responses and respond to at least two of your colleagues on two different days by suggesting additional factors that might have interfered with the pharmacokinetic and pharmacodynamic processes of the patients diagnosed with GAD. In addition, suggest different treatment options you would suggest to treat a patient with the topic of discussion.

Note: For this Discussion, you are required to complete your initial post before you will be able to view and respond to your colleagues’ postings. Begin by clicking on the Reply button to complete your initial post. Remember, once you click on Post Reply, you cannot delete or edit your own posts and you cannot post anonymously. Please check your post carefully before clicking on Post Reply!

Treatment of Generalized Anxiety Disorder

Generalized anxiety disorder (GAD) is a common psychiatric condition affecting a significant proportion of the population globally. Pharmacological agents are effective in treating GAD. Selective serotonin reuptake inhibitors (SSRIs) such as escitalopram and paroxetine are the first class of drugs used for GAD. SSRIs increase serotonin levels in the brain by inhibiting its reuptake. The liver metabolizes SSRIs after being absorbed in the gastrointestinal tract and eliminated via the renal system. Serotonin-noradrenaline reuptake inhibitors (SNRIs) are the other class of drugs used for GAD (Garakani et al., 2020; Tafet & Nemeroff, 2020). Examples of approved SNRIs include duloxetine, desvenlafaxine, venlafaxine, and levomilnacipran. They increase the serotonin and noradrenaline concentrations in the extracellular space. SNRIs are absorbed in the gastrointestinal system, metabolized in the liver by CYP450 enzymes, and excreted via the renal system.

Tricyclic antidepressants are the other class of drugs used for GAD, which increase the extracellular concentration of noradrenaline and serotonin. Tricyclic antidepressants undergo absorption in the gastrointestinal tract, metabolism by CYP enzymes in the liver, and excretion through the renal system. Imipramine is an example of an approved TCA for GAD. The other drug is bupropion, a noradrenaline-dopamine reuptake inhibitor, which increases noradrenaline and dopamine levels by inhibiting their reuptake. Bupropion is absorbed in the gastrointestinal system metabolized in the liver, and excreted through the renal system. Gabapentoids such as pregabalin and gabapentin are also highly effective for GAD. Gabapentoids have anxiolytic, anticonvulsant, and analgesic effect, hence, their use in GAD. Gabapentoids have a rapid absorption following oral intake and peak plasma levels reached between 0.7 and 1.3 hours (Fagan & Baldwin, 2023). They are metabolized in the liver and excreted via the renal system.

Antihistamines such as hydroxyzine are also effective for GAD. Antihistamines antagonize 5HT receptors to bring anxiolytic effects (Tafet & Nemeroff, 2020). Hydroxyzine is administered orally, absorbed via the gastrointestinal system, metabolized in the liver, and excreted through urine. Quetiapine is also another antipsychotic drug used for GAD, which antagonizes adrenoreceptors. Quetiapine is absorbed via the gastrointestinal tract, metabolized in the liver, and excreted in urine.

References

Fagan, H. A., & Baldwin, D. S. (2023). Pharmacological Treatment of Generalised Anxiety Disorder: Current Practice and Future Directions. Expert Review of Neurotherapeutics, 23(6), 535–548. https://doi.org/10.1080/14737175.2023.2211767

Garakani, A., Murrough, J., Freire, R., Thom, R., Larkin, K., Buono, F., & Iosifescu, D. (2020). Pharmacotherapy of Anxiety Disorders: Current and Emerging Treatment Options. Frontiers in Psychiatry, 11, 595584. https://doi.org/10.3389/fpsyt.2020.595584

Tafet, G. E., & Nemeroff, C. B. (2020). Pharmacological Treatment of Anxiety Disorders: The Role of the HPA Axis. Frontiers in Psychiatry, 11. https://www.frontiersin.org/articles/10.3389/fpsyt.2020.00443

Comparing and Contrasting Pharmacologic Options for the Treatment of Generalized Anxiety Disorder

A common and sometimes crippling mental health disease known as Generalized Anxiety Disorder, or GAD for short, is characterized by excessive and uncontrolled worry over a variety of ordinary concerns (Munir & Takov, 2022). GAD patients frequently have ongoing worry, restlessness, muscular tension, and other disturbing symptoms that have a major negative impact on their quality of life. Fortunately, there are several pharmaceutical treatments for GAD, each with specific advantages and disadvantages (Munir & Takov, 2022).

This discussion will go into the realm of pharmacotherapy for GAD, contrasting and comparing the various therapeutic choices to provide the audience with a better grasp of their mechanisms, effectiveness, side effects, and clinical practice issues.

Pharmacokinetics and Pharmacodynamics Related to Anxiolytic Drugs

Pharmacokinetics of Anxiolytic Drugs

Understanding the mechanisms of the pharmacodynamics and pharmacokinetic anxiolytic drugs used to treat GAD is essential. The onset, duration, and possible drug interactions of anxiolytic medicines are determined by their pharmacokinetic properties (Garakani et al., 2020). For instance, certain benzodiazepines, which are anxiolytics, are quickly absorbed and offer prompt relief from anxiety because of their early onset of action. Their quick metabolism and elimination, nevertheless, can cause problems with tolerance and reliance (Garakani et al., 2020). The levels of serotonin and norepinephrine in the brain are increased by selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), which have a delayed onset of action but provide a more long-lasting therapeutic impact. Because of their lesser potential for dependency, these medicines are favored for the long-term therapy of GAD (Garakani et al., 2020).

Pharmacodynamics of Anxiolytic Drugs

On the other hand, pharmacodynamics focuses on comprehending how neurotransmitter systems are impacted by anxiolytic drugs. Gamma-aminobutyric acid (GABA), a neurotransmitter that lowers neuronal excitability and promotes relaxation, is made more effective in inhibiting action by benzodiazepines (Nasir et al., 2020). Contrarily, SSRIs and SNRIs function by preventing serotonin and norepinephrine from being reabsorbed, increasing the amount of these neurotransmitters in synaptic clefts, and eventually regulating mood and anxiety (Nasir et al., 2020). While taking into account elements like the onset, duration of action, side effects, and potential interactions, it is essential to understand the pharmacokinetic and pharmacodynamic profiles of these drugs (Nasir et al., 2020).

Comparison of different Treatment Options for GAD

Psychotherapy vs. Medication

The goal of psychotherapy, including Cognitive-Behavioral Therapy (CBT), is to alter the thinking and behavior patterns that contribute to anxiety. It helps patients create coping mechanisms and anxiety-management techniques (Curtiss et al., 2021). Contrarily, medicine, such as Benzodiazepines and Selective Serotonin Reuptake Inhibitors (SSRIs), primarily tries to treat the signs and symptoms of anxiety (Melaragno, 2021).

While psychotherapy may take longer to produce observable results, its advantages frequently last after the end of care because patients gain the ability to control their anxiety on their own (Curtiss et al., 2021). Contrarily, medication provides more rapid relief and is frequently advised for people with severe or incapacitating symptoms. Although benzodiazepines entail a danger of dependency, medicines can also cause negative effects (Melaragno, 2021).

Cognitive-Behavioral Therapy (CBT) vs. Mindfulness-Based Approaches

While both CBT and mindfulness-based therapies are classified as psychotherapeutic interventions, their methods are different. The purpose of CBT is to recognize negative thinking patterns and challenge them. It is systematic and goal-oriented (Nakao et al., 2021). Being present in the moment and embracing thoughts and feelings without judgment are stressed in mindfulness-based treatments, such as Mindfulness-Based Stress Reduction (MBSR) (Velissaris et al., 2023).

CBT is a highly successful treatment for GAD and gives patients useful tools to deal with certain fears (Nakao et al., 2021). Mindfullness-based approaches encourage overall well-being and might be helpful for people who want to create a more pervasive calm and lessen stress. However, although mindfulness approaches might take time to show obvious improvements and may require constant practice, the organized form of CBT may not appeal to everyone (Velissaris et al., 2023).

In conclusion, the selection of the treatment for GAD should be based on the patient’s preferences, the severity of their symptoms, and whether or not they have any co-occurring illnesses. While some people might find the most relief from medicine, others could gain the most from psychotherapy. The best course of action is frequently a customized plan that takes into account the particular requirements and circumstances of each GAD patient.

References

Curtiss, J. E., Levine, D. S., Ander, I., & Baker, A. W. (2021). Cognitive-behavioral treatments for anxiety and stress-related disorders. Focus, 19(2), 184–189. https://doi.org/10.1176/appi.focus.20200045

Links to an external site.

Garakani, A., Murrough, J. W., Freire, R. C., Thom, R. P., Larkin, K., Buono, F. D., & Iosifescu, D. V. (2020). Pharmacotherapy of anxiety disorders: Current and emerging treatment options. Frontiers in Psychiatry, 11(595584). https://doi.org/10.3389/fpsyt.2020.595584

Links to an external site.

Melaragno, A. J. (2021). Pharmacotherapy for anxiety disorders: From first-line options to treatment resistance. FOCUS, 19(2), 145–160. https://doi.org/10.1176/appi.focus.20200048

Links to an external site.

Munir, S., & Takov, V. (2022, October 17). Generalized Anxiety Disorder (GAD). Nih.gov; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK441870/

Links to an external site.

Nakao, M., Shirotsuki, K., & Sugaya, N. (2021). Cognitive–behavioral therapy for management of mental health and stress-related disorders: Recent advances in techniques and technologies. BioPsychoSocial Medicine, 15(1). https://doi.org/10.1186/s13030-021-00219-w

Links to an external site.

Nasir, M., Trujillo, D., Levine, J., Dwyer, J. B., Rupp, Z. W., & Bloch, M. H. (2020). Glutamate systems in DSM-5 anxiety disorders: Their role and a review of glutamate and GABA psychopharmacology. Frontiers in Psychiatry, 11. https://doi.org/10.3389/fpsyt.2020.548505

Links to an external site.

Velissaris, S. L., Davis, M., Fisher, F., Gluyas, C., & Stout, J. C. (2023). A pilot evaluation of an 8-week mindfulness-based stress reduction program for people with pre-symptomatic Huntington’s disease. Journal of Community Genetics, 14(4), 395–405. https://doi.org/10.1007/s12687-023-00651-1